Kinetics of Aspartic Acid Isomerization and Enantiomerization in Model Aspartyl Tripeptides under Forced Conditions

Conrad, Uwe; Fahr, Alfred; Scriba, Gerhard K. E.

doi:10.1002/jps.22134

Cited by 17 publications

(12 citation statements)

References 34 publications

(42 reference statements)

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“…β‐Asp peptides were the major degradation products. After 240 h the β‐Asp peptides exceeded the α‐Asp peptides by a factor of 3.1–3.9 which is in good agreement with the literature data where a β/α‐Asp ratio of 4:1 has been reported for small peptides .…”

Section: Resultssupporting

confidence: 92%

“…In accordance with literature data , Asp isomerization accounted for the major degradation pathway at pH 10 at both temperatures studied. Furthermore, enantiomerization of all amino acids was observed proceeding in the order Asp > Ala > Phe.…”

Section: Discussionsupporting

confidence: 91%

“…In contrast, Conrad et al detected the diketopiperazines as minor products in incubations of the tripeptide l ‐Phe‐α‐ l ‐Asp‐GlyOH at 80°C and pH 10 while the major reaction pathways proved to be isomerization and enantiomerization of Asp . This difference could be attributed to the instability of the diketopiperazines at higher temperatures . Diketo‐piperazine formation was due to the attack of the N ‐terminal amino group on a succinimide carbonyl group of the Asu intermediate .…”

Section: Introductionmentioning

confidence: 93%

“…Studying the reactions of tripeptide l ‐Phe‐ l ‐Asn‐GlyOH at 25°C at alkaline pH, DeHart and Anderson noted formation of diastereomeric diketopiperazines as the major degradation products . In contrast, Conrad et al detected the diketopiperazines as minor products in incubations of the tripeptide l ‐Phe‐α‐ l ‐Asp‐GlyOH at 80°C and pH 10 while the major reaction pathways proved to be isomerization and enantiomerization of Asp . This difference could be attributed to the instability of the diketopiperazines at higher temperatures .…”

Section: Introductionmentioning

confidence: 99%

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Isomerization and epimerization of the aspartyl tetrapeptide Ala‐Phe‐Asp‐GlyOH at pH 10—A CE study

et al. 2013

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Isomerization and enantiomerization of Asp in the tetrapeptide Ala-Phe-Asp-GlyOH are studied at pH 10 and 80°C as well as 25°C. CE-MS allowed the distinction between α-Asp and β-Asp linkages in degradation products based on the ratio of the b and y fragment ions. Besides isomerization and enantiomerization of Asp, enantiomerization of Ala and Phe was also observed at both temperatures by chiral amino acid HPLC analysis using Marfey's reagent for derivatization. The rate of enantiomerization of the amino acids proceeded in the order Asp > Ala > Phe. The CE assay was validated with respect to linearity, LOQ, LOD, and precision and employed to characterize the time course of the degradation of the tetrapeptide upon incubation in borate buffer, pH 10. Isomerization to β-Asp peptides was identified as the major degradation reaction. The configuration of Asp or Ala affected the half-life of the starting peptide to a minor extent but did not influence the distribution of the individual products under equilibrium conditions at 80°C. Degradation at 25°C proceeded very slowly so that the equilibrium was not reached after 245 days.

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Section: Resultssupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Isomerization and epimerization of the aspartyl tetrapeptide Ala‐Phe‐Asp‐GlyOH at pH 10—A CE study

et al. 2013

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“…Using the unified equation, comparable activation enthalpies, activation entropies and Gibbs free activation energies as a measure of the enantiomerization barrier were obtained for both CD systems. Conrad and colleagues [95,96] analyzed the isomerization and enantiomerization kinetics of aspartyl model peptides employing a validated CE assay. In particular, at pH 10 rapid isomerization and enantiomerization was observed.…”

Section: Pharmaceutical Analysismentioning

confidence: 99%

Chiral electromigration techniques in pharmaceutical and biomedical analysis

Scriba

2011

Bioanal Rev

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Capillary electromigration techniques are often considered ideal methods for enantioseparations due to their high separation selectivity and flexibility. Thus, numerous methods employing a chiral selector as pseudostationary phase in a background electrolyte have been developed and applied for the chiral analysis of drugs in bulk ware, pharmaceutical formulations and biological matrices. Furthermore, electromigration techniques have been combined with spectroscopic methods such as nuclear magnetic resonance in order to understand the complexation of analytes by chiral selectors. The present review focuses on recent developments and applications of chiral electromigration techniques in pharmaceutical and biomedical analysis including examples illustrating analyte-selector complex formation or mechanistic studies which have been published between January 2009 and July 2011. Selector-mediated chiral separations clearly dominate while no applications of capillary electrochromatography to pharmaceutical or biomedical analysis have been reported during this period of time.

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How Isomerization and Epimerization in Long‐Lived Proteins Affect Lysosomal Degradation and Proteostasis

Julian¹

2021

Long‐lived Proteins in Human Aging and Disease

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Kinetics of Aspartic Acid Isomerization and Enantiomerization in Model Aspartyl Tripeptides under Forced Conditions

Cited by 17 publications

References 34 publications

Isomerization and epimerization of the aspartyl tetrapeptide Ala‐Phe‐Asp‐GlyOH at pH 10—A CE study

Isomerization and epimerization of the aspartyl tetrapeptide Ala‐Phe‐Asp‐GlyOH at pH 10—A CE study

Chiral electromigration techniques in pharmaceutical and biomedical analysis

How Isomerization and Epimerization in Long‐Lived Proteins Affect Lysosomal Degradation and Proteostasis

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